Category Archives: Fecal Microbiota Transplant (FMT)

Fecal microbiota transplantation (FMT) from a donor (heterologous) to treat recurrent Clostridium difficile infection (CDI) is safe and more effective than self (autologous) transplantation, according to data from a randomized controlled, double-blind clinical trial.

However, the results, published online August 23 in the Annals of Internal Medicine, also show that the treatment success rate in the control group varied substantially between two study locations, which suggests there are subtleties not yet understood with the approach.

The efficacy of FMT using donor stool to treat recurrent CDI has made headlines, but so far it has largely been tested only in open-label clinical trials and case series.

To complement these studies, Colleen R. Kelly, MD, from the Women’s Medicine Collaborative, The Miriam Hospital, Providence, Rhode Island, and coworkers enrolled 46 patients who had had at least three recurrences of CDI and who were treated with vancomycin for the most recent infection and randomly assigned them to receive donor or self stool preparations by colonoscopy.

The researchers assessed adverse events for 6 months after FMT, defining efficacy as cessation of diarrhea without the need for further antibiotics during the 8 weeks after the intervention. All stool was subject to microbiota analysis before and after FMT.

Twenty of the 22 patients in the donor FMT group (90.9%; 95% confidence interval [CI],69.2% – 97.8%) were clinically cured compared with

The nine patients who developed CDI after self FMT were then given donor FMT and were cured.

Microbiome analysis revealed no improvement in gut microbial diversity after self FMT, but restoration of a normal microbiota with donor FMT, including increases in Bacteroidetes and Firmicutes and decreases in Proteobacteria and Verrucomicrobia populations.

An unexpected finding was that patients treated autologously at Montefiore Medical Center in the Bronx, New York had a much higher cure rate than those treated autologously at The Miriam Hospital in Providence. Specifically, for Rhode Island, cure rate with donor FMT was 90.0% (CI, 51.8% – 98.7%) vs 42.9% (CI, 20.1% – 69.0%) with self FMT. For New York, cure rate with donor FMT was 91.7% (CI, 57.2% – 98.9%) compared with 90.0% (CI, 51.8% – 98.7%) with self FMT.

The researchers list clinical differences among the patients at the two sites that could explain the different responses to self FMT:

NY patients were infected longer, had more recurrences, and had more courses of fidaxomicin than did Rhode Island patients.

NY patients waited longer to be treated and took antibiotics longer before entering the study, and may have been cured at that time.

Fecal microbiomes among NY patients had more Clostridia species, which may have occupied niches for C difficile.

Limitations of the study include lack of inclusion of baseline antibody titers and infection severity, small sample size attributed partly to unwillingness of participants to risk assignment to the autologous group, and nonuniform stool doses. In addition, the researchers mention that some patients may be infected according to polymerase chain reaction (PCR)-based identification of the pathogen, but be asymptomatic, and that some patients may have diarrhea resulting from undiagnosed irritable bowel syndrome but also be infected with C difficile, according to PCR testing.

In an accompanying editorial, Elizabeth L. Hohmann, MD, from Massachusetts General Hospital in Boston, points out another limitation, that “the population enrolled in this trial was younger (mean age, 50 years) and seemed healthier and more adventurous than most patients with recurrent CDI.” In contrast, about 60% of her patients with whom she discusses FMT are older than 60 years, and 30% are older than 75 years. However, the investigators had to recruit patients younger than 75 years to comply with FDA regulations to consider FMT as an investigational new drug.

No serious adverse events were reported. The researchers conclude, “FMT using fresh donor stool administered via colonoscopy after a course of vancomycin was effective at preventing further CDI episodes in patients with multiply recurrent infection.” They call for additional investigation to identify types of patients most likely to benefit from FMT using donor stool.

Dr Hohmann regards the differing response rates to autologous FMT at the two study sites as instructive, underscoring the value of conducting a rigorous controlled trial even when the tested technology has proven itself in other types of investigations. “Their results prompt us to ask again whether microbial manipulation has any as-yet unappreciated health benefits or risks and whether there are preferred microbiomes for specific human populations or locales,” she concludes.

Medicine, like all science, is dynamic and evolving—that’s why it is referred to as “the practice of medicine.”

Accepted treatments of one era might be discarded later as “pseudoscience.” What is considered “experimental” today might become the standard of treatment tomorrow.

Fortunately, there is something called peer review and scientific standards. Also, most health care providers have embraced the process of gathering as much evidence as possible instead of treating patients like lab rats.

There is no safe substitute for the intimate, one-on-one relationship between a patient and a physician. This will continue to be true as long as doctors remember that medicine is a science and an art, full of both expected outcomes and surprising solutions.

The phrase “Nine out of 10 doctors recommend…” is often used to promote widely accepted treatments, so that one outlier doctor must be responsible for all the rather wacky treatments that we other physicians get asked about every week. And although some of these treatments seem beyond bizarre, they can also be incredibly interesting.

At least they were to the three physicians listed in this article’s byline, including
Dr. H. Eric Bender, who says his fascination with peculiar medical practices started in medical school. During one of his early rotations, he was shocked to learn that not only could he order leeches for a patient in the hospital but he could specify where they were to be placed as well: left leg, right arm or whole body. (In case you’re wondering, to precisely “aim” a leech, place it in a small cup with a very small hole cut in the bottom. That hole is then aligned with the area on the patient requiring blood removal and voilà! Bloodthirsty segmented worms are suddenly hard at work.
(Dr. Bender does not recommend trying this at home.)

Now, thanks to our internet-sparked society of do-it-yourselfers, Bender’s fascination with the unconventional cure has continued to grow as he has contemplated conversations with his patients and researched a wide range of (seemingly) ridiculous but sometimes effective remedies.
“Unfortunately, the physician’s oath to “do no harm” has been replaced in many
clinics with “do clean up this mess.”

For example, a physician or two in the not so distant past recommended that children smoke tobacco to treat pica, a condition in which people feel compelled to chew on non-nutritious substances like rocks, sand or glass. Some doctors over the years suggested that patients use cocaine and heroin to remedy toothaches and persistent cough, respectively. (In addition to references, the book includes pictures as evidence.) Alcohol has been recommended to pregnant women for its health benefits—Guinness beer is rich in iron—and not just by Irish physicians. Others practicing medicine have suggested using hookworms to cure asthma (causing dangerous infections).

The list of dangerous substances, organisms and animal byproducts that people have used over the years to treat everything from low libido to sexually transmitted diseases goes on and on. Fortunately, most of the practices did not, as further research demonstrated the dangers of many of them.

“Weird medicine” is not limited to just medical practices and treatments. A look into the medical literature reveals that it is replete with research and studies that aren’t particularly well-designed or are far-fetched to the point of absurdity.

Some fascinating practices seemed like terrible ideas but are actually so well-supported by research that they are considered the gold standard for treatment of certain illnesses.

As an example, consider that antibiotics frequently kill good bacteria while also killing the bad bacteria doctors are trying to eliminate.

“Good” bacteria suppress the growth of bad bacteria. So when the good bacteria are wiped out, many individuals develop a type of intestinal infection known as Clostridium difficile
(or C. diff ). C. diff is often difficult to treat with antibiotics, since they typically caused the problem in the first place. Fortunately, one treatment has a high rate of s
uccess: fecal transplantation. Yes, you read that correctly. Doctors place stool from a donor inside the patient’s gastrointestinal system. Intuitively, you might think putting my feces into your gut would cause serious infections, but the donated good bacteria help eradicate infection.

IHow about maggots instead? Maggot therapy involves using those little legless larvae to prevent a wound infection. Maggots selectively target and eat dead tissue that is difficult to remove surgically without taking healthy tissue with it. Although doctors have been aware of this fact since at least the 1930s, this treatment was not regularly used for decades, particularly as antibiotic use to treat and manage wounds rose in popularity. However, after a recent “rediscovery” of maggot therapy, more than 800 health care institutions use it today. You can be sure pharmaceutical companies are already working on a way to charge exorbitant prices for the little larvae.

Patients performing their own research online can spark informative conversations with their doctors, even if they do sometimes suggest things that make a person want to scream, or puke.

Nevertheless, although “Dr. Google” is punctual and doesn’t require a co-pay, it is still not qualified to diagnose and treat.

There is no safe substitute for the intimate, one-on-one relationship between a patient and a physician. This will continue to be true as long as doctors remember that medicine is a science and an art, full of both expected outcomes and surprising solutions.

So to our patients: Be wary of charlatans but keep an open mind. Bring all your questions to a physician and ask away. To our fellow physicians: Listen to your patients. Talk with them, not to them. And remember: If you can’t do any good, at least do no harm.

H. Eric Bender, Murdoc Khaleghi and Bobby Singh are the authors of 1 Out of 10 Doctors Recommends: Drinking Urine, Eating Worms, and Other Weird Cures, Cases, and Research from the Annals of Medicine.

Pick a disease or disorder, and somebody, somewhere, has said that a probiotic supplement—an over-the-counter, unregulated pill usually filled with a single strain of friendly gut bacteria—might cure it, whether it’s cancer, obsessive-compulsive disorder, or a yeast infection.

But there’s very little evidence that probiotic supplements do any good. “There’s a lot of promise here but not a lot of proof yet,” said Cliff McDonald, associate director for science at the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion.

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CDC Reports:

Half a million people a year are infected with C. diff in the U.S., the CDC estimates, with 29,000 annual deaths related to the diarrheic bacterium. More than 65 percent of C. diff infections involve exposure in a health-care facility, according to a 2015 study, creating more than $4.8 billion in excess health-care costs at acute-care facilities alone.

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C. diff. Treatments On The Horizon:

To Learn More About ALL C. diff. Clinical Trials In Progress Click On The Following Link:

Seres Therapeutics, a microbiome-based biopharmaceutical company in Cambridge, Mass., is developing a pill, subject to a rigorous approval process under the Food and Drug Administration, to tackle recurrent Clostridium difficile. (The digestive system’s microbiome is the community of healthy gut bacteria that normally reside in the body.)

Seres aims to put the science behind a proven treatment of recurrent C. diff, fecal transplants, in a pill, which wouldn’t require a colonoscopy. Like probiotic supplements, it’s a gut bacteria product. Unlike the supplements, by the time it’s available it will have gone through the FDA wringer. It will contain about 50 strains of bacteria proven effective in treating C. diff and will require a doctor’s prescription.

Recurrent C. diff is an obvious entry point for Seres, said Chief Executive Officer Roger Pomerantz. “We asked, what is the lowest-hanging fruit?” But it’s hardly the end. The company has built a microbiome library of 14,000 strains of human bacteria it hopes will help it treat a range of diseases, eventually without needing feces at all. Seres has embarked on the research with some pretty lofty goals, including finding treatments for obesity, liver disease, and cancer. It has partnerships with Massachusetts General Hospital, the Mayo Clinic, Memorial Sloan Kettering Cancer Center, and other respected medical institutions. “We will figure out exactly what’s wrong with the microbiome, design a drug, and then pull the organisms out with our library, never touching a human donation,” Pomerantz said. Seres’s lead product candidate, SER-109, will treat recurrent C. diff with four capsules taken orally instead of with transplants. While fecal matter is the raw material for the pills, the final product consists only of the spores necessary to treat the infection, which will have been extracted and purified. SER-109 is expected to become the first oral microbiome therapy approved by the FDA, though Seres declined to predict exactly when it will arrive. Results from the latest trials are due by midyear, and Phase 3 trials are scheduled to follow later in the year. Seres hopes to follow up quickly with SER-287, a drug to treat ulcerative colitis, which could be the first microbiome drug to treat a chronic disease, and SER-262, to treat primary C. diff before it turns into the recurrent kind.

Other companies are racing to collect enough data for FDA approval, but right now Seres, which is publicly traded, looks to be the one to beat. “Seres is probably going to be the first one that’s going to knock at the FDA’s door,” said Mohan Iyer, chief business officer at Second Genome, a microbiome company studying how to treat disease with the compounds produced by gut bacteria instead of the gut bacteria themselves.

“SER-109 is poised to be first-in-class among fecal microbiota transplant-derived drugs,” Joseph Schwartz, an analyst at Leerink Partners, wrote in a May report. The report says the latest trial results “wowed the Street” but warns that the company could still be held back by “disappointing clinical data” and obstacles in the regulatory process.

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Another top contender is Rebiotix. Its RBX2660 is also designed to treat recurrent C. diff but, unlike SER-109, is administered with an enema; an oral version is in development. The treatment also differs significantly from Seres’s in formulation, including thousands of kinds of microbes from the donor’s stool, compared with SER-109’s 50 or so, as many as could be preserved and some of which haven’t even been identified.

“We make sure we have a minimum concentration of certain kinds that we know the patients lack,” CEO Lee Jones said. “But we don’t identify all of them. There’s no way to do that.” A recent study estimated that 1014 bacteria are in the human gut, most of which have never been isolated. Jones said the drug could hit the market by 2018.

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UPDATES:

The medications have been shown to be similarly effective—with no C. diff-associated diarrhea for 29 of 30 of Seres’s patients and 27 of 31 of Rebiotix’s, in the companies’ latest results—and equally safe. Adverse reactions for both are limited to such problems as moderate diarrhea and abdominal cramping, which could be from the C. diff itself. Both have been designated as “breakthrough therapies” by the FDA, allowing for an expedited approval process, and both are likely soon to provide an at-home alternative to fecal transplants.

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Point Of View:

“I don’t know who is going to make it across the line first,” said Gail Hecht, director of gastroenterology and nutrition at Loyola University Medical Center and chairwoman of the American Gastroenterological Association for Gut Microbiome Research & Education. Hecht has attended a Seres advisory board meeting but doesn’t have a financial interest in the company. “It is indeed a race,” she said.

Seres does have at least one distinct market advantage. “Patients have different preferences,” Hecht observes, but “in general, people don’t particularly like enemas.”

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Human Fecal Transplants:

For nearly two thousand years, doctors have looked to this unlikeliest of places for medicine. One of the earliest documented applications is from the fourth-century Chinese medical doctor Ge Hong, whose “yellow soup” recipe to treat diarrhea included a healthy person’s dried or fermented feces. Sixteen hundred years later, in 1958, patients infected with C. diff received the first known human fecal transplants.

Stool Bank Information:

Today the effectiveness of fecal transplants (formally known as fecal microbiota transplants) to treat recurrent C. diff is supported by a long list of studies, with researchers attributing the results to the restoration of the microbiome. OpenBiome, a nonprofit stool bank, shipped 1,828 treatments in 2014, a number that ballooned to 7,140 treatments in 2015 and looks to be eclipsed this year, with 4,323 treatments shipped to its clinical partners through May 31. And these numbers don’t take into account the transplants performed through directed fecal donations.

This Episode: Rebiotix: The Leader in Unlocking the Benefits of Microbiota Restoration Therapy (MRT) “

With Our Guest: Lee Jones, Founder and CEO, Rebiotix

Join us today on C. diff. Spores and More discuss Rebiotix
with Rebiotix Founder, CEO Lee Jones. Listen in as we learn more about
the History, Company profile, the problems they are solving, and product information. Lee will explain What is the microbiome? Their first product RBX 2660 – addressing C. diff, with the Rebiotix platform called MRT (Microbiota Restoration Therapy) and how MRT is different
and much more.

MORE ABOUT OUR GUEST:

Lee Jones, CEO and Founder of Rebiotix Inc., is an experienced medical technology executive and serial entrepreneur. With deep experience in the medical devices industry and in managing and advising academic scientists on commercialization efforts, Rebiotix marks her first foray into biotechnology. She is leading a fast-paced effort to develop a new way of treating disease through Microbiota Restoration Therapy (MRT). The company’s first MRT is a biologic drug targeted at recurrent Clostridium difficile infection.
Rebiotix Founder, President, CEO, Privately held biotechnology company founded in 2011 Developing a new category of drugs to harness the human microbiome to treat disease; involves transplantation of live human-derived microbes; first target is recurrent Clostridium difficile infection, Led pioneering work with the US Food and Drug Administration to develop a new classification for the product – RBX2660 – completed Phase 2 clinical testing.

Through their interviews, the C Diff Foundation mission will connect, educate, and empower many worldwide.

Questions received through the show page portal will be reviewed and addressed by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP, Dr. Fred Zar is a Professor of Clinical Medicine, Vice Head for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency at the University of Illinois at Chicago. Over the last two decades he has been a pioneer in the study of the treatment ofClostridium difficile disease and the need to stratify patients by disease severity.

With Our Guest: James Mcllory

Listen to the PodCast available from the JUNE 7TH C.diff Spores and More episode as we discussed current C.difficile infection objectives for hospitals within the United Kingdom with James McIlroy, a medical student and founder of a not-for-profit stool bank based within the University of Aberdeen in Scotland

MORE ABOUT OUR GUEST:

James McIlroy is a senior medical student at the University of Aberdeen in Scotland. Previously, he earned his Bachelors in Medical Sciences with Honors in human Physiology at the University of Edinburgh. At the present time, James is undertaking a prestigious fellowship at the Royal Society of Edinburgh. During his time at medical school, James identified an unmet need for safe access to fecal microbiota transplantation (FMT) within the United Kingdom. He subsequently established a not-for-profit community interest company called EuroBiotix CIC, which seeks to support clinicians within the UK National Health Service provide FMT.

Through their interviews, the C Diff Foundation mission will connect, educate, and empower many worldwide.

Questions received through the show page portal will be reviewed and addressed by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP, Dr. Fred Zar is a Professor of Clinical Medicine, Vice Head for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency at the University of Illinois at Chicago. Over the last two decades he has been a pioneer in the study of the treatment ofClostridium difficile disease and the need to stratify patients by disease severity.

A small pilot study featuring 15 pediatric patients found that 14 out of 15 with recurringC. difficile infections reported no additional episodes more than 3 months following the procedure, reported Aneeq Malik, BS, of Morehouse School of Medicine in Atlanta, and colleagues. They presented their results at the Pediatric Academic Societies (PAS) annual meeting.

Overall, 15 children underwent the procedure — seven male and eight female, with a mean age of 7.9 years, with at least three episodes of C. difficile within a 3-month period. The patients ranged from 21 months to 18 years, and had an average of 5.7 diarrheal stools per day, as well as an average of 3.3 courses of antibiotics within a 12-month period. Seven also had ulcerative colitis, while two apiece had Crohn’s disease and GERD.

Following a stool transplant from a pre-screened stool bank, patients were followed up via phone at 24 hours and 1 week after the procedure and were instructed to see their GI doctor at 1 and 3 months afterwards. Three patients were hospitalized a month following the procedure for diarrhea, dehydration and rCDI. However, only one patient was actually found to have clinical symptoms of C. difficile plus a positive stool test.

Limitations to the study included the size of the sample, as well as the fact that clinical symptoms were based on self-report and that several of their patients had underlying GI conditions. Co-author Lilly Immergluck, MD, also of Morehouse School of Medicine, said at the presentation that she considered that a strength of the study — that the success rate of the procedure was high, despite the patients’ other conditions.

Brandt said that despite limitations, he still characterized the procedure as exciting and said the evaluation of the microbiome will be very important for the future of this research.

“I think in the future we probably will not be using stool – we’ll be using some product derived from stool – because we don’t really know what the protecting organism is,” he said.

To read the article in its entirety please click on the following link:

On Tuesday, March 8th our guest, Glenn Taylor — Head Microbiologist – joined us to discuss

CLICK ON THE Cdiff radio LOGO BELOW TO ACCESS THE PODCAST OF THIS EPISODE **

Our guest, Glenn Taylor – Microbiologist at the Taymount Clinic just outside London in the UK, joined us to discuss this important topic. Glenn has spent more than five years researching the commensal colonization of bacteria in the human digestive system. The Taymount Clinics are known internationally as a specialist center for the production of tested, certified, high quality gut bacteria and effective, efficient implant techniques Researching intestinal bacteria since 2006, the Taymount Clinic is now a recognized world leader in applying Fecal / Faecal Microbiota Transplant or FMT treatment procedures to create a “normal” bacterial environment in patients with a broad range of conditions. The Taymount clinic provides FMT treatment to normalize gut bacteria in patients with a Clostridium difficile infection.

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